Caffeine disposition after oral doses

Bonati, Maurizio; Latini, Roberto; Galletti, Ferruccio; Young, John F; Tognoni, Gianni; Garattini, Silvio

doi:10.1038/clpt.1982.132

Cited by 355Coffee research and impactsPharmacogenetics and Drug MetabolismPlant-based Medicinal Research

Caffeine disposition after oral doses

Bonati, Maurizio, Latini, Roberto, Galletti, Ferruccio, Young, John F, Tognoni, Gianni, Garattini, Silvio·1982·Clinical Pharmacology and Therapeutics

DOI 10.1038/clpt.1982.132

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Abstract

Caffeine (TMX) disposition was studied in mean after 1, 5, and 10 mg/kg in water, as mocha coffee (1.54 mg/kg) and as a soft drink (0.22 mg/kg). TMX and its metabolites were analyzed in plasma and urine by high-pressure liquid chromatography. The design permitted confirmation of most of the partial results in various experimental settings and contributed new data on the metabolic disposition of TMX, with specific reference to main dimethylxanthine metabolite found in plasma, paraxanthine (1,7-dimethylxanthine). Different analysis methods were compared for the calculated parameters (absorption and elimination rate constants and renal clearance)to assess the consistency of results. The kinetics of TMX and of its dimethylated metabolites in plasma were described with a model that used an analogdigital hybrid computing system. In addition to providing a comprehensive profile of TMS disposition in the healthy adult, the results indicate tha TMX exhibits dose-independent kinetics at the levels at which man normally takes TMX.

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The kinetics of caffeine have been reported to be linear in doses up to 10 mg/kg bw.
“The kinetics of caffeine have been reported to be linear in doses up to 10 mg/kg bw (Bonati et al., 1982), whereas a later study claimed non-linearity beginning at doses as high as 500 mg, corresponding to about 7.1 mg/kg bw (Kaplan et al., 1997).”
From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Bonati et al., 1982

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“The low degree of excretion of unchanged drug is in agreement with previous reports (Bonati et al., 1982; Newton et al., 1981; Tang-Liu et al., 1982).”
BackgroundResult
The effects of caffeine on caffeine users and non-users
Kuznicki, J. T., & Turner, L. S. (1986) · Physiology & Behavior · doi:10.1016/0031-9384(86)90197-6 · Cited by 76 · see citing works
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“Numerous factors such as dosage, dose formulation, and route of administration can impact the pharmacokinetics of CAF (5,27).”
Background
Pharmacokinetics of caffeine and its metabolites in plasma and urine after consuming a soluble green/roasted coffee blend by healthy subjects
Martínez-López, S., Sarriá, B., Baeza, G., Mateos, R., & Bravo, L. (2014) · Food Research International · doi:10.1016/j.foodres.2014.05.043 · Cited by 72 · see citing works
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“, nonfiltered coffee with a limited caffeine content) (22), and the relatively high alcohol intake (mainly wine) in this population.”
Background
Neuroprotective Effect of Caffeine in Alzheimer’s Disease
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Background
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“Our data indicate that: (1) the elimination of caffeine is impaired in cirrhosis, characterized by a reduction in plasma clearance and a prolongation in caffeine half-life; (2) the oral 13C-CBT using a single 1-hour measure correlates very closely with plasma caffeine clearance; (3) cirrhotic subjects show significant…”
Result
Influence of caffeine ingestion on perceived mood states, concentration, and arousal levels during a 75-min university lecture
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Method
Kinetic and Dynamic Description of Caffeine
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Background
Use of the BioDis to generate a physiologically relevant IVIVC
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“(10) report an elimination half-life of 14 min in mouse brain and plasma for a synthetic chlorogenic acid, whereas the half-life of CAF in human plasma is several hours (3, 14, 27).”
BackgroundMethod
Biotransformation of caffeine by cDNA-expressed human cytochromes P-450
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Multiple dose pharmacokinetics of caffeine administered in chewing gum to normal healthy volunteers
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Background
Insights on the Health Benefits of the Bioactive Compounds of Coffee Silverskin Extract
Fernandez-Gomez, B., Lezama, A., Amigo-Benavent, M., Ullate, M., Herrero, M., Martín, M. Á., Mesa, M. D., & del Castillo, M. D. (2016) · Journal of Functional Foods · doi:10.1016/j.jff.2016.06.001 · Cited by 58 · see citing works
“Caffeine was present in the urine of both groups of rats, which is in agreement with 461 other studies that described incomplete biotransformation in humans (Bonati et al., 1982; 462 Rodopoulos, Wisén, & Norman, 1995).”
Result
Does caffeine counteract alcohol-induced impairment? The ironic effects of expectancy.
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Assessment of hepatic function
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“Considering that subjects ingested half their daily caffeine 1 h prior to cognitive testing (thus maximizing plasma caffeine concentration during the tasks [29,36,37]), the results of the four-choice reaction time and the Visual Vigilance tests offer three interpretations: (1) caffeine ingestion has no cognitive effec…”
Result
Effect of allopurinol on caffeine disposition in man.
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“sumably by a number of distinct liver enzymes, which produce a variety of demethylated and 8hydroxylated metabolites detectable in the plasma and/or urine (Bonati et al., 1982; Callahan et al., 1982; Tang-Liu et al., 1983).”
Background
Caffeine and stress alter salivary α‐amylase activity in young men
Klein, L. C., Bennett, J. M., Whetzel, C. A., Granger, D. A., & Ritter, F. E. (2010) · Human Psychopharmacology Clinical and Experimental · doi:10.1002/hup.1126 · Cited by 54 · see citing works
“After capsule administration, participants were asked to rest for 20 min to allow for adequate caffeine absorption and to ensure that participants were completing the mental arithmetic task when plasma caffeine levels were on the ascending limb of the absorption curve (Bonati et al., 1982; Liguori et al., 1997); blood…”
BackgroundMethod

Pharmacokinetics of Caffeine and Dimethylxanthines in Plasma and Saliva
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Sympathomimetic effects of paraxanthine and caffeine in humans*
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Time to Recover From Daily Caffeine Intake
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Simple and reliable CYP1A2 phenotyping by the paraxanthine/caffeine ratio in plasma and in saliva
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Authors: Bonati, M., Latini, R., Galletti, F., Young, J. F., Tognoni, G., & Garattini, S.
Affiliations: National Center for Toxicological Research (US)
Corresponding author: Bonati, Maurizio
ORCID: Bonati, Maurizio
Latini, Roberto
Galletti, Ferruccio
Garattini, Silvio
Venue: Clinical Pharmacology and Therapeutics
Publisher: Wiley
Published: 1982-07
Volume: 32
Issue: 1
Pages: 98-106
ISSN: 0009-9236 (ISSN-L)
1532-6535
DOI: 10.1038/clpt.1982.132
OpenAlex: W2047855828
Cited by: 353
References: 0
Citations by year: 2026: 7 · 2025: 10 · 2024: 10 · 2023: 8 · 2022: 8 · 2021: 9 · 2020: 8 · 2019: 7 · 2018: 13 · 2017: 14 · 2016: 11 · 2015: 13 · 2014: 12 · 2013: 10 · 2012: 20
FWCI: 8.12
Type: journal article
Language: en
Open access: closed
Locations: Clinical Pharmacology & Therapeutics (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology › Coffee research and impacts
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Plant-based Medicinal Research
Keywords: caffeine, oral administration, caffeine metabolites, paraxanthine, 1,7-dimethylxanthine, dimethylxanthines, absorption rate constant, elimination rate constant, renal clearance, plasma kinetics, coffee, soft drinks, pharmacokinetic modeling
MeSH terms: Administration, Oral, Adult, Biotransformation, Caffeine, Carbonated Beverages, Coffee, Humans, Kinetics, Male

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Caffeine disposition after oral doses

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